The involvement of ADH in Alcohol Intolerance Poster project - Biokemi 1 – 2009 Andy Vincent & Johan Dunevall Institutionen för kemi, Göteborgs Universitet Box 462, Göteborg (Sverige) Summery Alcohol intolerance is a genetic condition caused by the polymorphism in the genes encoding the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). In afflicted individuals ADH2 has been attributed as an over active enzyme that increases the levels of the toxin acetealdehyde through the oxidation of ethanol, which causes physilogical reactions such as facial flushing. Inltroduction Alcohol intolerance can have several meanings depending on how the alcohol has come into contact with the body. Skin related allergies and rashes are results of exposure to alcohol through contact of the skin but here the effects of alcohol intolerance is focused on the consumption of ethanol. The major symptom of the intolerance is facial flushing due to blood vessel vasodilation (Eriksson, 2001), the result of the consumption of small amounts of alcoholic beverages. Alcohol flushing after light drinking is triggered mainly by severe acetaldehydemia (Yokoyama, 2003). This effect is experienced in large groups of Asian populations but has also been seen to a lesser extent in Western populations. Other effects of alcohol consumption in the affected individual can be nausea, headaches, and occasional skin swelling and itchiness. Genetic information Although ADH participates in the effects of alcohol intolerance, the relevance of the ADH for the actions of alcohol is not documented as much as with ALDH. ADH has more than 20 different isoenzymes with greatly differing kinetic properties in vitro (Sherman). On chromosome 4, the enzyme is encoded by three adjacent gene loci, ADH1, ADH2, and ADH3. The kinetic differences among ADH2 isozymes are more evident than those of the ADH3 isozymes, where the alcohol-intolerant individual would have a more active ADH2 isozyme, increasing the levels of acetaldehyde. So it is probable that a defect in ADH2 is a partial cause of the intolerance. Many Asians lack enzyme activity of ALDH2 and have highly active enzyme activity of ADH2, attributed to point mutations within both structural genes (Anonymous, 2003). Hence, the expression of these two enzyme mutations could determine the alcohol tolerance among Asian populations. Referenser Anonymous. (2003). Diabetic Vasculopathy and Alcohol Tolerance Trait in Type 2 Diabetes. diabetes care, volume 26, number 1, 246. Eriksson, C. J. (2001). Functional Relevance of Human ADH Polymorphism. alcoholism: clinical and experimental research, Sherman, D. I. (u.d.). Association ofrestriction fragment length polymorphism in alcohol. Yokoyama, T. (2003). Alcohol Flushing, Alcohol and Aldehyde Dehydrogenase Genotypes,. Cancer Epidemiology, Biomarkers & Prevention, Metabolism The oxidation of ethanol to acetate is a two step process catalyzed by two enzymes. The first step is the oxidation of ethanol to acetaldehyde catalyzed by alcohol dehydrogenase. The second step is the further oxidation to acetate by aldehyde dehydrogenase. In both of these reactions NAD + is reduced to NADH to balance the redox reaction. The rate of alcohol oxidation is the crucial factor that determines the metabolic consequences during alcohol intoxication. A defect in one or both of these enzymes would cause high levels of toxic acetaldehyde. Facial flushing: the before and after picture of an Asien individual that consumed alcohol. ADH: the structure of the enzyme, with a substrate analog shown in green.